BioNTech Diagnostics GmbH, a subsidiary of BioNTech AG, announces the publication of further study data which again document the superiority of the in-vitro diagnostic MammaTyper® test (CE marked IVD) over immunohistochemical detection methods (IHC) [1]. “The special feature of the currently published performance evaluation study is the fact that, for the first time, results of gene expression analysis with MammaTyper® were not only compared with results of manual microscopic analysis of immunohistochemical specimens but also with computer-assisted image analysis“, emphasized Dr. Sierk Pötting, Managing Director of BioNTech Diagnostics GmbH.

The study used formalin-fixed, paraffin-embedded (FFPE) routine biopsy samples from breast cancer patients who had participated in a randomized neoadjuvant study [2]. These samples were analyzed with the three methods prospectively and retrospectively. In the currently published study, as well as in previous publications [3,4], MammaTyper® demonstrated a significant superiority in the quantitative determination of the proliferation marker MKI67 (Ki-67) compared to IHC. Therefore MammaTyper® achieves significantly higher specificity than IHC in the identification of a possible pathological complete remission after neoadjuvant therapy. Prof. Dr. Hans-Peter Sinn, University of Heidelberg and head of the study summarized the results as follows: “The study demonstrates that MammaTyper® is able to reliably prognosticate tumor proliferation activity and the response to neoadjuvant therapy. That means patients may be spared unnecessary treatments“.

The classification of tumors in luminal, basal and HER2-amplified subtypes by the immunohistochemical markers estrogen receptor (ER), progesterone receptor (PR), HER2 and the proliferation marker Ki-67 provides the basis of biological subtyping and (neo)adjuvant therapy decisions for mammary carcinomas [5]. Moreover, since the 2013 St Gallen Conference, the proliferation marker Ki-67 has also been confirmed for the definition of the intrinsic subtypes Luminal A and Luminal B-like [6]. An earlier study in a neoadjuvant setting was able to show that high Ki-67 values are consistently associated with higher rates of pathological complete remission [11]. The current standard method for detection of the Ki-67 proliferation marker as well as the biomarkers ER and PR is manual microscopic immunohistochemistry which has, however, been debated for some time due to the great intra- and inter-observer variability [7,8].

Results of the determination of biomarkers ESR1 (ER) and PGR (PR) in the currently published study again confirm the good correlation of MammaTyper® with immunohistochemistry results, showing a slightly higher correlation of MammaTyper® and computer-assisted immunohistochemistry (ER/ESR1: 91.23 %, p<0.0001; PR/PGR: 92.9 %, p < 0.0001). In contrast, MammaTyper® and computer-assisted IHC image analysis achieved , as expected, moderate correlation (Spearman’s r = 0.5; p = 0.0001) in the detection of the proliferation marker MKI67 (Ki-67). However, correlated with clinical progress data, MammaTyper® proved to be significantly superior to IHC – especially in predicting the response to neoadjuvant therapy derived from MKI67 determination.

The current study shows again that MammaTyper® is an interesting and reliable alternative to the currently customary IHC detection methods. Moreover, MammaTyper® offers the possibility for an improved prediction of pathological complete remission after neoadjuvant chemotherapy.

Therefore, MammaTyper could contribute to a well-founded therapy decision which could spare breast cancer patients unecessary treatments in the future.

5. Goldhirsch, Winer, Coates, et al. (2013). “Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013.” Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 24(9): 2206-2223.

6. Coates AS et al. (2015) Tailoring therapies – improving the management of early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 24(9): 2206-2223.

7. Polley, Leung, Gao, et al. (2015). “An international study to increase concordance in Ki67 scoring.” Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc.